Decoding bone-inspired and cell-instructive cues of scaffolds for bone tissue engineering

Bone fractures are common occurrence in clinical settings, creating a high demand for effective repair material. Unfortunately, limited graft availability, donor site morbidities, unpredictable clinical outcomes, immunologic reactions, infection risks, and geometrical mismatching concerns hampered tissue graft use and underscored the need for scaffolds for more effective bone reconstructions due to their tunable properties. Significant progress has been carried out in past decade in the fields of nanoceramics synthesis, bioconjugate chemistry, and composite material processing. This review outlines hierarchical structures and biology of bone tissue, materialistic components of scaffolds (bioceramics, polymers, bioactive drugs), featured scaffolding strategies (nanofibers, hydrogels, aerogels, bioprinting, and fiber-reinforced composite), and emphasis that hierarchical and physiochemical characteristics of bone should be used as an inspiration for scaffold design. This review discussed how differences in materiobiological aspects of scaffolds, such as polymer/bioceramic nanocomposite, mineralized nanocomposite, matrix-rich nanocomposite, 3D microenvironmental cues, pore space cues, mechanical cues, usage of physical stimulation (magnetic, electroactive, and photoactivated cues), surface cues (wettability, roughness, textured, and surface charge), and biointerface cues (cell–biomaterial interactions, cell-selective homing, and cell regulatory strategies) modulate cellular and biological response for bone tissue engineering. This study further outlines the challenges and benefits of integrating materiobiological cues of scaffolds for bone tissue engineering.